Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE.

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

The epidemiology of acute pancreatitis in Tasmania over a 12-year period: Is this a disease of disadvantage?

BACKGROUND: The global incidence of acute pancreatitis (AP) is increasing, but little information exists about trends in Australia. This study aimed to describe incidence trends, along with clinical and socio-demographic associations, in the state of Tasmania over a recent 12-year period. METHODS: The study cohort was obtained by linking clinical and administrative datasets encompassing the whole Tasmanian population between 2007 and 2018, inclusive. Pancreatitis case definition was based on relevant ICD-10 hospitalization codes, or elevated serum lipase or amylase in pathology data. Age-standardised incidence rates were estimated, overall and stratified by sex, aetiology, and Index of Relative Socio-economic Disadvantage (IRSD). RESULTS: In the study period, 4905 public hospital AP episodes were identified in 3503 people. The age-standardised person-based incidence rate across the entire period was 54 per 100,000 per year. Incidence was inversely related to IRSD score; 71 per 100,000 per year in the most disadvantaged quartile compared to 32 in the least disadvantaged. Biliary AP incidence was higher than that of alcohol-related AP, although the greatest incidence was in "unspecified" cases. There was an increase in incidence for the whole cohort (average annual percent change 3.23 %), largely driven by the two most disadvantaged IRSD quartiles; the least disadvantaged quartile saw a slight overall decrease. CONCLUSION: This is the first Australian study providing robust evidence that AP incidence is increasing and is at the upper limit of population-based studies worldwide. This increased incidence is greatest in socio-economically disadvantaged areas, meriting further research to develop targeted, holistic management strategies.

Intestinal dysbiosis and inflammation in children with repaired esophageal atresia.

OBJECTIVES: This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS: A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS: Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS: Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.

Cystic fibrosis liver disease in the new era of cystic fibrosis transmembrane conductance regulator (CFTR) modulators.

Cystic fibrosis liver disease (CFLD) is characterised by a wide heterogenity of manifestations and severity. It represents a major cause of morbidity in people with cystic fibrosis (PwCF), which will be of increasing relevance as survival increases in the new era of cystic fibrosis care. No medical therapy currently available has evidence to treat or prevent progression of liver disease. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators may be transformative on pulmonary, nutritional and quality of life, but direct effect on long term liver disease outcomes is not yet established. Drug-associated hepatic adverse effects may be common, and clinician familiarity with drug-monitoring recommendations is essential. Longitudinal studies are required to understand the effect of CFTR modulators on the incidence and natural history of CFLD, including with early treatment initiation, in established advanced liver disease, and post liver transplantation.

New consensus definition on defining and measuring care for children with paediatric feeding disorder.

AIM: This study addresses the absence of a definition of care for children with feeding disorders, limited agreement on key performance indicators (KPIs), and the lack of data linked to those KPIs. METHODS: Clinicians, consumers and researchers involved in outpatient feeding care in New South Wales (NSW), Australia were invited to participate in a two-Phase study. In Phase 1, a modified Delphi method was used. Two rounds of voting resulted in a new consensus definition of a multidisciplinary paediatric feeding clinic. Three further rounds voting determined relevant KPIs. In Phase 2, the KPIs were piloted prospectively in 10 clinics. RESULTS: Twenty-six clinicians, consumers and researchers participated in Phase 1. Participation across five voting rounds declined from 92% to 60% and a valid definition and KPI set were created. In Phase 2, the definition and KPIs were piloted in 10 clinics over 6 weeks. Data for 110 patients were collected. The final KPI set of 28 measures proposed covers clinical features, patient demographics and medical issues, parent-child interaction and outcome measures. CONCLUSIONS: A new definition of a multidisciplinary paediatric feeding clinic is now available, linked to a standardised KPI set covering relevant performance measures. These proved viable in baseline data collection for 10 clinics across NSW. This sets a foundation for further data collection, systematic measurement of care provision and outcomes, and research needed to deliver care improvement for children with paediatric feeding disorder.

Does the Nutritional Intake and Diet Quality of Children With Chronic Kidney Disease Differ From Healthy Controls? A Comprehensive Evaluation.

OBJECTIVE: Children with chronic kidney disease (CKD) experience many obstacles to achieving optimal dietary intake. Dietary intake patterns remain unexplored or poorly described. This study compares nutritional intake and diet quality of Australian children with CKD to controls. METHODS: A food frequency questionnaire captured intake data and was compared to controls. Nutritional intake was determined using individualized nutrient reference values, and diet quality described using the Australian Guide to Healthy Eating and the Australian Child and Adolescent Recommended Food Score. RESULTS: Children with CKD (n = 36) and controls (n = 82) were studied. Children with CKD had lower weight and height z scores, but higher body mass index (P < .0001 for all parameters). Children with CKD had adequate energy intake, and excessive protein and sodium intake (336% and 569%). They were significantly less likely to meet requirements for vitamin A (P < .001), thiamine (P = .006), folate (P = .01), vitamin C (P = .008), calcium (P < .0001), iron (P = .01), magnesium (P = .0009), and potassium (P = .002). No child met recommended vegetable intake; however, less than half of children with CKD met fruit (44%), grains (31%), and dairy serves (31%). They were also less likely to meet recommended fruit and dairy serves (P = .04 and P = .01, respectively). Non-core foods provided 36% of energy, and although comparable to controls, was contributed more by takeaway foods (P = .01). CONCLUSION: Children with CKD have reduced nutritional intake of key nutrients and consume more takeaways than controls. Attention to increasing core foods, limiting sodium intake, and managing restrictions while promoting nutrient density appears necessary.

Bone health in children with recurrent and chronic pancreatitis: A multi-center cross sectional analysis.

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied. METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2. RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively). CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE.

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. RESULTS: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. CONCLUSIONS: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

Molecular Dynamics and Theratyping in Airway and Gut Organoids Reveal R352Q-CFTR Conductance Defect.

A significant challenge to making targeted cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies accessible to all individuals with cystic fibrosis (CF) are many mutations in the CFTR gene that can cause CF, most of which remain uncharacterized. Here, we characterized the structural and functional defects of the rare CFTR mutation R352Q, with a potential role contributing to intrapore chloride ion permeation, in patient-derived cell models of the airway and gut. CFTR function in differentiated nasal epithelial cultures and matched intestinal organoids was assessed using an ion transport assay and forskolin-induced swelling assay, respectively. CFTR potentiators (VX-770, GLPG1837, and VX-445) and correctors (VX-809, VX-445, with or without VX-661) were tested. Data from R352Q-CFTR were compared with data of 20 participants with mutations with known impact on CFTR function. R352Q-CFTR has residual CFTR function that was restored to functional CFTR activity by CFTR potentiators but not the corrector. Molecular dynamics simulations of R352Q-CFTR were carried out, which indicated the presence of a chloride conductance defect, with little evidence supporting a gating defect. The combination approach of in vitro patient-derived cell models and in silico molecular dynamics simulations to characterize rare CFTR mutations can improve the specificity and sensitivity of modulator response predictions and aid in their translational use for CF precision medicine.

Children With Cystic Fibrosis Have Elevated Levels of Fecal Chitinase-3-like-1.

Although chitinase-3-like-1 (CHI3L1), predominately produced by epithelial cells and macrophages, is relevant to pulmonary disease in cystic fibrosis (CF), fecal levels have not yet been assessed in children with CF. Fecal CHI3L1 was measured with a commercial immunoassay using fecal samples provided by children with CF and healthy control (HC) children. Higher median (interquartile range) fecal CHI3L1 levels were seen in the 52 children with CF than in the 35 controls: 15.97 (3.34-50.53) ng/g versus 2.93 (2.13-9.27) ng/g ( P = 0.001). Fecal CHI3LI did not differ according to sex. In the children with CF, fecal CHI3L1 levels did not correlate with growth parameters nor were the levels affected by pancreatic insufficiency. Children with CF had higher fecal CHI3L1 levels, suggesting underlying gut inflammation. Further work is required to confirm the current findings and to ascertain the longer-term significance of elevated CHI3L1.

Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.

OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors.

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. RESULTS: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001). CONCLUSIONS: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.

Australasian paediatric gastroenterologist practices of coeliac disease diagnosis before and during the COVID-19 pandemic.

AIM: To explore the perceptions and practices of Australasian paediatric gastroenterologists in diagnosing coeliac disease (CD) before and during the COVID-19 pandemic. METHODS: Paediatric gastroenterologists in Australasia were invited via email to complete an anonymous online questionnaire over a 2-week period in 2021. RESULTS: The questionnaire was completed by 39 respondents: 33 from Australia and six from New Zealand (NZ) equating to a 66% response rate. Thirty-four (87%) of the 39 respondents reported they currently practised non-biopsy diagnosis of CD in eligible children, while the rest diagnosed CD using biopsy confirmation only. All NZ respondents practised non-biopsy CD diagnosis. A majority of responders (76%) who practised non-biopsy CD diagnosis followed the 2020 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. Twenty-two (56%) respondents reported that they started using a non-biopsy CD diagnosis protocol before the pandemic and did not change their practice during the pandemic, 10 (26%) started diagnosing non-biopsy CD during the pandemic, 5 (13%) stated their practices of CD were not impacted by the pandemic and 2 (5%) did not respond on whether the pandemic changed their practice. CONCLUSION: The majority of Australasian gastroenterologist respondents reported they routinely utilised the 2020 ESPGHAN diagnostic criteria in eligible children; half of them started prior to the pandemic and another quarter started this approach due to the pandemic. A minority of practitioners routinely rely only on biopsy confirmation to diagnose CD.

Demographics and risk factors for pediatric recurrent acute pancreatitis.

PURPOSE OF REVIEW: Approximately 20-30% of children who experience one episode of acute pancreatitis will have at least one additional episode. For some children, pancreatitis recurs multiple times and in a few years is followed by the diagnosis of chronic pancreatitis. Identifying risk factors for recurrent episodes and disease progression is critical to developing therapeutic interventions. RECENT FINDINGS: Obesity is driving an increase in biliary stone disease and severe acute pancreatitis. Recurrent acute pancreatitis (RAP) may lead to the development of diabetes through autoimmune mechanisms. Cystic fibrosis or CFTR-related disorders may present as RAP and CFTR modulator therapy can increase or decrease the risk of acute pancreatitis in these populations. Children with Crohn disease have a three-fold risk of acute pancreatitis over the general population while children with ulcerative colitis are at increased risk for pediatric autoimmune pancreatitis, a disorder that may be distinct from autoimmune pancreatitis described in adults. Obstructive jaundice in the absence of identified mechanical factors may be a presenting sign of pediatric autoimmune pancreatitis. SUMMARY: Pediatric RAP is a painful condition that leads to gland destruction and functional insufficiency. Risk factors are being clarified but preventive treatments remain elusive.

Vascular Complications in Pediatric Pancreatitis: A Case Series.

ABSTRACT: We reviewed INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) database for splanchnic venous thrombosis or arterial pseudoaneurysms to determine the incidence, risk factors and outcomes of peripancreatic vascular complications in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Of 410 children with diagnostic imaging studies, vascular complications were reported in five (1.2%); two had ARP, three CP. The vascular events were reported during moderately severe or severe acute pancreatitis (AP) in four, mild AP in one. Venous thrombosis occurred in four, arterial pseudoaneurysm (left gastric artery) in one. Two patients with venous thrombosis were treated with anticoagulant, one achieved recanalization (splenic vein). In two patients who did not receive anticoagulants, one re-canalized. No adverse effects were observed with anticoagulants. The child with pseudoaneurysm underwent aneurysmal coiling. Anti-coagulants appear to be safe in children with acute pancreatitis, their long-term benefit needs to be further investigated.

Resuscitating Cardiopulmonary Resuscitation Training in a Virtual Reality: Prospective Interventional Study.

BACKGROUND: Simulation-based technologies are emerging to enhance medical education in the digital era. However, there is limited data for the use of virtual reality simulation in pediatric medical education. We developed Virtual Doc as a highly immersive virtual reality simulation to teach pediatric cardiopulmonary resuscitation skills to medical students. OBJECTIVE: The primary objectives of this study were to evaluate participant satisfaction and perceived educational efficacy of Virtual Doc. The secondary aim of this study was to assess the game play features of Virtual Doc. METHODS: We conducted a prospective closed beta-testing study at the University of New South Wales (Sydney, Australia) in 2018. All medical students from the 6-year undergraduate program were eligible to participate and were recruited through voluntary convenience sampling. Participants attended a 1-hour testing session and attempted at least one full resuscitation case using the virtual reality simulator. Following this, participants were asked to complete an anonymous postsession questionnaire. Responses were analyzed using descriptive statistics. RESULTS: A total of 26 participants were recruited, consented to participate in this study, and attended a 1-hour in-person closed beta-testing session, and 88% (23/26) of participants completed the anonymous questionnaire and were included in this study. Regarding participant satisfaction, Virtual Doc was enjoyed by 91% (21/23) of participants, with 74% (17/23) intending to recommend the simulation to a colleague and 66% (15/23) intending to recommend the simulation to a friend. In assessment of the perceived educational value of Virtual Doc, 70% (16/23) of participants agreed they had an improved understanding of cardiopulmonary resuscitation, and 78% (18/23) agreed that Virtual Doc will help prepare for and deal with real-life clinical scenarios. Furthermore, 91% (21/23) of participants agreed with the development of additional Virtual Doc cases as beneficial for learning. An evaluation of the game play features as our secondary objective revealed that 70% (16/23) of participants agreed with ease in understanding how to use Virtual Doc, and 74% (17/23) found the game play elements useful in understanding cardiopulmonary resuscitation. One-third (7/23, 30%) found it easy to work with the interactive elements. In addition, 74% (17/23) were interested in interacting with other students within the simulation. CONCLUSIONS: Our study demonstrates a positive response regarding trainee satisfaction and perceived educational efficacy of Virtual Doc. The simulation was widely accepted by the majority of users and may have the potential to improve educational learning objectives.

Cystic Fibrosis-related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD). METHODS: A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center). RESULTS: One hundred sixty-six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] -6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2-1.3] vs 0.4 [0.1-0.9]; P = 0.002); gastrointestinal indications (0.09 [0-0.2] vs 0 [0-0.05]; P < 0.001); and other indications (0.05 [0-0.2] vs 0 [0-0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06-6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05-3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01-3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01-4.52]; P = 0.04), as well as CF-related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55-4.47]; P = 0.001). CONCLUSIONS: Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF-related bone disease and diabetes.

Does Combined Multichannel Intraluminal Impedance and pH (MII-pH) Testing Improve Clinical Outcomes in Children With Gastroesophageal Reflux Disease?

OBJECTIVES: The aim of the study was to investigate the role of combined multichannel intraluminal impedance and pH (MII-pH) testing in clinical management of children with gastroesophageal reflux disease (GERD) by exploring the impact of treatment changes made based on MII-pH testing results on symptoms and quality of life outcomes. METHODS: All patients (<18 years) referred to the Sydney Children's Hospital for MII-pH testing were recruited. Patients were classified by acid suppression therapy (AST) status (on AST and off AST) and changes in medical and surgical management were evaluated. Validated questionnaires (Pediatric Gastroesophageal Symptom and Quality of Life Questionnaire and Infant Gastroesophageal Reflux Questionnaire Revised) were administered at baseline at the time of MII-pH testing, and 4 weeks after treatment changes were made and questionnaire scores were compared. RESULTS: Of the 45 patients recruited, 24 patients (53.3%) were off AST and 21 patients (46.7%) were on AST. MII-pH testing led to medication changes in 30 patients (66.7%). This included 15 of 24 (62.5%) in those off AST and 15 of 21 (71.4%) in those on AST. More than 98% of patients who had treatment changes showed a significant improvement in both symptoms and quality of life scores. CONCLUSIONS: Our study is one of the first pediatric studies to evaluate the clinical validity of MII-pH testing in the pediatric population referred for suspected GERD, and its ability in guiding clinical management. Our study has shown that treatment decisions guided by and based on results of MII-pH testing led to a significant improvement in symptoms and quality of life in infants and children with GERD.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

OBJECTIVES: The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). METHODS: Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. RESULTS: Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. CONCLUSIONS: In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.